Stabilized Heptapeptide A7R for Enhanced Multifunctional Liposome-Based Tumor-Targeted Drug Delivery

被引：67

作者：

Ying, Man ^{[1
,2
]}

Shen, Qing ^{[1
,2
,3
]}

Liu, Yu ^{[1
,2
]}

Yan, Zhiqiang ^{[4
]}

Wei, Xiaoli ^{[1
,2
,5
]}

Zhan, Changyou ^{[1
,2
,6
]}

Gao, Jie ^{[1
,2
]}

Xie, Cao ^{[1
,2
]}

Yao, Bingxin ^{[1
,2
]}

Lu, Weiyue ^{[1
,2
,3
,5
]}

机构：

[1] Fudan Univ, Sch Pharm, Dept Pharmaceut, Shanghai 201203, Peoples R China

[2] Fudan Univ, Key Lab Smart Drug Delivery, Minist Educ, Shanghai 201203, Peoples R China

[3] Fudan Univ, State Key Lab Mol Engn Polymers, Shanghai 200433, Peoples R China

[4] E China Normal Univ, Sch Chem & Mol Engn, Shanghai Engn Res Ctr Mol Therapeut & New Drug De, Inst Biomed Engn & Technol, Shanghai 200062, Peoples R China

[5] Fudan Univ, Collaborat Innovat Ctr Brain Sci, State Key Lab Med Neurobiol, Shanghai 200032, Peoples R China

[6] Fudan Univ, Sch Basic Med Sci, Dept Pharmacol, Shanghai 200032, Peoples R China

来源：

ACS APPLIED MATERIALS & INTERFACES | 2016年 / 8卷 / 21期

基金：

中国国家自然科学基金;

关键词：

(D)A7R; liposomes; stability; tumor; targeted drug delivery; ENDOTHELIAL GROWTH-FACTOR; D-PEPTIDE LIGAND; VASCULOGENIC MIMICRY; VEGF(165) BINDING; CELLS; NANOPARTICLES; NEUROPILIN-1; ANGIOGENESIS; NANOCARRIERS; VASCULATURE;

D O I：

10.1021/acsami.6b01300

中图分类号：

TB3 [工程材料学];

学科分类号：

0805 ; 080502 ;

摘要：

(L)A7R (ATWLPPR) is a heptapeptide with high binding affinity in vitro to vascular endothelial growth factor receptor 2 (VEGFR2) and neuropilin-1 (NRP-1) overexpressed on glioma, glioma vasculogenic mimicry and neovasculature. However, its tumor targeting efficacy is significantly reduced in vivo due to proteolysis in blood circulation. To improve the in vivo stability and targeting efficacy, the retro inverso isomer of (L)A7R ((D)A7R) was developed for glioma-targeted drug delivery. (D)A7R was expected to have a similar binding affinity to its receptors in vitro (VEGFR2 and NRP-1), which was experimentally confirmed. In vivo, (D)A7R-modified liposomes achieved improved glioma-targeted efficiency than did (L)A7R-modified liposomes. After loading a chemotherapeutic agent (doxorubicin), (D)A7R-modified liposomes significantly inhibited subcutaneous model tumor in comparison to free doxorubicin, plain liposomes and (L)A7R-modified liposomes. In summary, the present study presented the potential of a proteolytically stable D-peptide ligand for in vivo tumor-targeted drug delivery.

引用

页码：13232 / 13241

页数：10

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